The monoclonal antibody natalizumab significantly reduced cerebrospinal fluid markers of intrathecal inflammation in patients with progressive multiple sclerosis, according to data from an open-label, single-arm, phase IIa study.
Dr. Jeppe Romme Christensen and his colleagues from Copenhagen University Hospital, Denmark, found that 60 weeks of treatment with natalizumab (Tysabri) was associated with significant reductions from baseline in cerebrospinal fluid (CSF) osteopontin, as well as other CSF biomarkers of inflammation, axonal damage, demyelination, and CSF mononuclear cells. The study also may have helped to establish the feasibility of using CSF biomarkers in proof-of-concept trials.
The study, which included 12 patients with primary progressive multiple sclerosis and 12 with secondary progressive multiple sclerosis, showed similar treatment outcomes for both disease courses (Neurology 2014 March 28 [doi: 10.1212/WNL.0000000000000361]).
The authors said this was, to their knowledge, the first study to use a CSF biomarker as the primary endpoint. They noted that CSF osteopontin was a sensitive and dynamic marker of intrathecal inflammation, and its use enabled a smaller sample size and duration of study. "Osteopontin is a pleiotropic proinflammatory cytokine that is abundantly expressed in MS ... lesions, and is associated with the development of a progressive disease course," they wrote.
The study was supported by Biogen Idec, the Danish MS Society, the Danish Council for Strategic Research, and Brdr. Rønje Holding. Most authors declared honoraria and support from various pharmaceutical companies.